Gene profiling reveals hydrogen sulphide recruits death signaling via the N-methyl-D-aspartate receptor identifying commonalities with excitotoxicity

Chen, M. J. et al. (2011) Gene profiling reveals hydrogen sulphide recruits death signaling via the N-methyl-D-aspartate receptor identifying commonalities with excitotoxicity. Journal of Cellular Physiology, 226(5), pp. 1308-1322. (doi: 10.1002/jcp.22459)

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Recently the role of hydrogen sulphide (H<sub>2</sub>S) as a gasotransmitter stimulated wide interest owing to its involvement in Alzheimer's disease and ischemic stroke. Previously we demonstrated the importance of functional ionotropic glutamate receptors (GluRs) by neurons is critical for H<sub>2</sub>S-mediated dose- and time-dependent injury. Moreover N-methyl-D-aspartate receptor (NMDAR) antagonists abolished the consequences of H<sub>2</sub>S-induced neuronal death. This study focuses on deciphering the downstream effects activation of NMDAR on H<sub>2</sub>S-mediated neuronal injury by analyzing the time-course of global gene profiling (5, 15, and 24 h) to provide a comprehensive description of the recruitment of NMDAR-mediated signaling. Microarray analyses were performed on RNA from cultured mouse primary cortical neurons treated with 200 µM sodium hydrosulphide (NaHS) or NMDA over a time-course of 5–24 h. Data were validated via real-time PCR, western blotting, and global proteomic analysis. A substantial overlap of 1649 genes, accounting for over 80% of NMDA global gene profile present in that of H<sub>2</sub>S and over 50% vice versa, was observed. Within these commonly occurring genes, the percentage of transcriptional consistency at each time-point ranged from 81 to 97%. Gene families involved included those related to cell death, endoplasmic reticulum stress, calcium homeostasis, cell cycle, heat shock proteins, and chaperones. Examination of genes exclusive to H<sub>2</sub>S-mediated injury (43%) revealed extensive dysfunction of the ubiquitin-proteasome system. These data form a foundation for the development of screening platforms and define targets for intervention in H<sub>2</sub>S neuropathologies where NMDAR-activated signaling cascades played a substantial

Item Type:Articles
Glasgow Author(s) Enlighten ID:Melendez Romero, Dr Alirio
Authors: Chen, M. J., Peng, Z. F., Manikandan, J., Melendez Romero, A. J., Tan, G. S., Chung, C. M., Li, Q.-T., Tan, T. M., Deng, L. W., Whiteman, M., Beart, P. M., Moore, P. K., and Cheung, N. S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Cellular Physiology
Journal Abbr.:J. Cell Physiol.
ISSN (Online):1097-4652
Published Online:22 February 2011
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
462311Therapeutic potential of Sphingosine Kinase blockage in allergic anaphylaxis.Alirio Melendez RomeroMedical Research Council (MRC)G0700794Institute of Infection Immunity and Inflammation